Process for producing thyroid-gland extracts.



@TATEd PATENT UFFICE.

ERNST HOENNICKE, OF DRESDEN, GERMANY.

PROCESS FOR PRODUCING THYROTD-GLAND EXTRACTS.

nuances. We Brewing. Application filed November 27,

Specification of Letters Piftent.

1907, Serial No. 404,099. Renewed April 27, 1912. Serial No. 693,550.

Patented Aug. 27, 1912.

Gland Extracts, of which the following is a description.

The present invention consists of a process for separating out and producing the colloidal contents of the vesicles'contained in macerations of the thyroid gland and of the cell colloids mixed therewith which have passed into a brine solution ora condltlon of suspension in brine.

Colloidal bodies are capableof assuming two conditions. These bodies do not actually enter into solution like salt or sugar, but what appears as a-solution is really suspension in very finely divided particles in vthe liquid. This condition is known as the sol condition. In opposition to this condition is the gel condition, 2. e. a condition of more or less concentrated coagulatipn or a stringy or gelatin-like condition. All albuminsbodies are colloidal bodies. The more easily such bodies pass into or exist in the sol 'condition and the greater the diliiculty in converting them to the gel condition, therless marked are the colloidal properties of the same and the contrary is also the case, the more diliicult it is to reduce a colloidal substance to the sol condition and the more easy it is to bring it to the gel condition the more marked are'it's colloidal properties. The former is the case with the contents of the vesicles or the albumin bodies forming the inner secre tions, while the latter is the case with the ccll-albumins, 2'. e. the albumin bodies of the cells of the glands.

The object of the" 'present invention is to utilize these different properties of the two' bbdies to separate the same from each other.

Filters made of clay, porcelain, infusorial earth and the like, such as the Berkefeld, Ncrtmeyer, Kitasate, Chamberland,

Pasteur and other filtersare capable of re-v taining the finest corpuscular elements of the liquid filtered, and are therefore very generally employed for the purpose of filtcring liquidsto free them of germs.

In filtering the saline mace-rations of the thyroid glands, it has been observed that, apart from the sediment of the maceration being filtered, a brownish stringy residue remains, which is not a sediment, but will not pass through the filter. This residue was originally considered to be merely one of filtration, but it has now been ascertained that this is not the case. Apparently this residue consists of dissolved cellular substances, which have passed into the liquid of the maceration together with the contents of the vesicles and have been dissolved therein.

A comparative examination of the residue and the fluid filtered, shows that the former consists of cell-albumins which coagulate completely on being heated, while the albuminfiltered, will not coagulate evenv at 100 and will-merely opalesce after ha ving been boiled-for a, considerable time,

without, however, leaving any sediment,

even after having been allowed to stand. for a long period. Therefore although the residue, of course contains slight traces of non-coagulable albumin, the filtrate is entirely free from the coagulable albumin of the residue. This is also proved bythe fact that, in filtering liquids of equal initial conccntrationand in spite of varying amounts of albumin in the mace-rations being filtered, due to the extraction of varying amounts of cellular constituents by. the saline solution-a filtered liquid having a constant amount of albumin is always obtained. it

Thus by a purely physical method a result is obtained which, on examination would appear to be as follows The liquid of the maceration contains dissolved cellular constituent parts in addi tion to the contents of the vesicles, which cannot always be'avoided, because many of the thyroid glands are damaged while be ing removed. These cellular constituent parts, which were originally protoplasms of a gelatinous nature, a-re for the most part gradually brought into the sol state in the brine of the macerat-ing liquid, while the contents .of the vesicles, which are of course also colloidal substances, are naturally, for physiological reasons, already in this condition. In filtering ,as above the loids from each other, has hitherto not been 45 the vesicles beobtained', but also the cellular albumin may be obtained in a pure conditwo colloidal substances are believed to be separated, the separation being due=to the properties of the filtering material. Further experiments have shown that. the extreme difi'usibility of the contents of the vesicles in comparison with the cellular constituent parts, as assumed, is not only a fact, but a fact of great practical value; The contents of the vesicles and the cellular con stituent parts vary so greatly in their adfility or capability of diifusion, 'that'by ialysis the crystalloids may not only be separated from the colloids, but the latter may be separated from each other. While, for instance the contents of the vesicles will not pass through a hogs bladder, they will pass through parchment paper, which on the other hand, will not allow cellular albumin to pass. Thus separating diaphragms or partitions of clay, porcelain, in-

. fusorial earth or'the like are equal to parchment paper;v Accordingly the dialysis may take the place of filtration, 2'. e. if the material of the glands is placed in a properly 725 closed bag-of parchment paper or in a porous cylinder of one of the above mentioned materials, 'in a physiological solution of common salt, the contents of the vesicles alone will passthrough the wall and the liquid at the outside will be the finished product. This method of employing the Berkefeld filters and their equivalents, as

above mentioned, as an animal membrane, whetherforthe purpose of filtration or for the dialysis, for separating the dissolved colemployed for the production of thyroid gland preparations, and is novelv for this purpose. The following advantages accrue filter. -The filtrate will be the contents of from the employment:-1. There can be no possibility-of any chemical influence beihg exercised'ont-he. albumin substances. 2. If

the maceration liquid is freed from sediment proper, by previous decanting or filtering, not only-will the pure contents of tion, by repeated washing of the. residue'of the filtration, Itis also not denaturized, for it retains its solubility. As. an exa. A thyroid glandmaceration. in salt so v lution is rendered free'of sediment by being repeatedly filtered'through the same paper filter and isclearly filtered, whereupon the clear result' is filtered thrqughhl-Berkefeld the vesicles and the residue after having been repeatedly washed or dialyzed', will be cellular-albumin. T In its crude state the maceration contains:(a) some sediment as also small solidparticles, (b) dissolved cel- -lular albumin in a certain proportion,

(0) all the vesicle albumin. By repeated filtering throu h n ordinar filter the sediment mentioned under (2:) will be eliminated and the solution wil be clear. 'In the cylinder of porous clay. or of any of the other materials mentioned and the bag or cylinder hung or placed a physiological solution of common salt to which 0.5% of .phenol has been added. The contents of the vesicles only will pass into the solution.

Experiments with the substance of the other organs have shown that, with the aid of the employment of the materials mentioned ,as animal membrances, in the form of filters or dialyzing apparatuses, the cellular albumin which has passed into the condition known as that of S01 or in a state of finely divided particles inls'uspepsion, may be entirely separatedowing to its marked colloidal propertiesfrom the diffusible inner secretions.

Further experiments with pure animal membranes, have shown that not all are suit-able for the dialysis. Thus hogs bladder is unsuited while the small intestines are Well suited for the purpose. Thus, if sausages containing thyroid glands or other organs are made, and suspended in a physiological solution of'common salt, the inner secretion will diffuse into the salt solution. Dissolved hemoglobin does not possess the same capability of diffusion as the inner secretions, but almost the same. If the material is previously dried, the preparation will be obtained free from blood and of a pure yellow.

The product of-the process is the contents of the vesicle in a liquid state, and by means of the process any iniurious alteration of the original condition of the same, which might reduce its effectiveness is entirely prevented. The product is employed in many cases as a remedy and as a material for physiological experiments with animals. The cellalbumins' are looked upon as a by-product and may be employed for medical and technical purposes.

I claim as my invention 1. A process for separating out and obtaining in a pure liquid state the colloidal vesicle contents or inner secretions of thy,- roid glands, which consists in passing a maceration of the said organs in brine solution, 'in which the cellular colloids are in the condition of finely divided particles in suspension. through .a filter which allows the vesicle contents only to pass while restraining the colloids of the associated tissues.

2. A process for separating out and ob-- taining in a pure liquid state the colloidal vesicle contents or inner secretions of thyroid glands, which consists in passing anmceration of the same organs in brine solution, in which the cellular colloids are in restraining the colloids of the associated tissues.

In testimony whereof I aflix my signature in the presence of two Witnesses.

- ERNST HOENNIGKE Witnesses:

O'r'ro WOEFF, Y. GEORGE DUNNING. 

